238 research outputs found
A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro
No full textL-Asparaginases (ASNases) have been used as first line drugs for
paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than
40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi
(ErAII) type II ASNases currently used in the clinics are characterized
by high in vivo instability, short half-life and the requirement of
several administrations to obtain a pharmacologically active
concentration. Moreover, they are sensitive to proteases (cathepsin B
and asparagine endopeptidase) that are over-expressed by resistant
leukaemia lymphoblasts, thereby impairing drug activity and
pharmacokinetics. Herein, we present the biochemical, structural and in
vitro antiproliferative characterization of a new EcAII variant, N24S.
The mutant shows completely preserved asparaginase and glutaminase
activities, long-term storage stability, improved thermal parameters,
and outstanding resistance to proteases derived from leukaemia cells.
Structural analysis demonstrates a modification in the hydrogen bond
network related to residue 24, while Normal Mode-based geometric
Simulation and Molecular Dynamics predict a general rigidification of
the monomer as compared to wild-type. These improved features render
N24S a potential alternative treatment to reduce the number of drug
administrations in vivo and to successfully address one of the major
current challenges of ALL treatment: spontaneous, protease-dependent and
immunological inactivation of ASNase
Uintah High School Wrestling Team
No full textUintah High School wrestling team members are from left, front row, D. Richens, E. Billings, D. Price, Curt Smuin, D. Huber, Chris Walker, William Kurtz, John Baker, Scott Potter and Dan Firth. Center row, Cliff Grua, Scott Wall, J. Jacobson, D. Bursch, A. Thacker, Pl. Coon, M. Brown, L. Burns, C. Woollwy, Scott Bigelow, Tim McDonald, John Price. Back row, Mike Keele, C. Harrison, Scott Bingham, Quentin Price, D. Hatch, Mike Murray, R. Gray, Gary Duke, Alan Cooper, R. Jorgensen, R. Logan, W. Lohoff, Brent Merrell and Dean Martinsen
The Helicobacter pylori Ferric Uptake Regulator (Fur) is essential for growth under sodium chloride stress
No full text
Polymorphisms in the Intermediate Region of VacA Impact <i>Helicobacter pylori</i> -Induced Disease Development
No full textABSTRACT
Helicobacter pylori
is the etiological agent of diseases such as gastritis, gastric and duodenal ulcers, and two types of gastric cancers. While some insight has been gained into the etiology of these diverse manifestations, by and large, the reason that some individuals develop more severe disease remains elusive. Recent studies have focused on the roles of
H. pylori
toxins CagA and VacA on the disease process and have suggested that both toxins are intimately involved. Moreover, CagA and VacA are polymorphic within different
H. pylori
strains, and particular polymorphisms seem to show a correlation with the development of particular disease states. Among VacA polymorphisms, the intermediate region has recently been proposed to play a major role in disease outcome. In this article, we describe a detailed sequence analysis of the polymorphic intermediate region of
vacA
from strains obtained from a large South Korean population. We show that polymorphisms found at amino acid position 196 are associated with more severe disease manifestations. Additionally, polymorphisms found at amino acid position 231 are linked to disease in strains that carry the non-EPIYA-ABD allele of CagA. Collectively, these data help explain the impact of the VacA intermediate region on disease and lead to the hypothesis that there are allele-driven interactions between VacA and CagA.
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Research Advances in the Study of Campylobacter, Helicobacter & Related Organisms
No full textpathogens that remain a major cause of acute gastroenteritis and gastric disease, respectively. The 16th International Workshop on Campylobacter, Helicobacter and Related Organisms (CHRO) was organized by Erin Gaynor and Christine Szymanski and wa
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